Da-Bu-Yin-Wan Improves the Ameliorative Effect of DJ-1 on Mitochondrial Dysfunction Through Augmenting the Akt Phosphorylation in a Cellular Model of Parkinson’s Disease

Abstract

Da-Bu-Yin-Wan (DBYW) is recorded originally in China over six centuries ago, and it is used to treat Parkinson’s disease (PD) clinically in recent decades. DJ-1 is a homodimeric protein linked to early-onset PD, and found in the mitochondria. In addition, DJ-1 could protect the cells by regulating gene transcription and modulating the Akt signal pathways. Therefore, in this research, we aimed to investigate the ameliorative effect of DBYW on mitochondria in the view of the DJ-1 and Akt signaling. Rat adrenal pheochromocytoma cell line PC-12 was transfected with the plasmid pcDNA3-Flag-DJ-1 (pDJ-1). Subsequently, PC-12 cells were exposed to the PD-related mitochondrial toxin (1-methyl-4-phenylpyridinium) without/with the DBYW. After transfected with the plasmid pDJ-1, the 1-methyl-4-phenylpyridinium-induced toxicity was decreased, and the DJ-1 expression in protein level was increased. DJ-1 overexpression not only increased the mitochondrial mass, but also improved the total ATP content. Moreover, Akt phosphorylation was augmented by DJ-1 overexpression. Additionally, DBYW enhanced the above effects. Conclusively, these findings indicate that DBYW promotes the ameliorative effects of DJ-1 on mitochondrial dysfunction at least through augmenting the Akt phosphorylation in 1-methyl-4-phenylpyridinium-treated PC-12 cells.

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

“…The protective effects of BYQZF on mitochondrial function have been confirmed in in vitro and in vivo studies (Zhang et al, 2013;Zhang et al, 2018;Gai et al, 2019); parkin was found to play an important role in this process. However, the mechanisms by which BYQZF ameliorates mitochondrial dysfunction via parkin are unclear.…”

“…Our previous studies showed that Da-Bu-Yin-Wan ameliorates MPTP-induced behavioral impairment, increases the expression of tyrosine hydroxylase in the substantia nigra, and prevents loss of substantia nigra dopaminergic neurons in a PD mouse model (Gong et al, 2014). Moreover, Da-Bu-Yin-Wan and/or Qian-Zheng-San significantly increase ATP levels and complex I activity in the midbrain tissue of PD model mice (Zhang et al, 2013), and BYQZF reduced mitochondrial damage and improved the mitochondrial morphological structure in a cellular model of PD (Zhang et al, 2018;Gai et al, 2019). These studies suggest that BYQZF had neuroprotective effects on mitochondrial function and may be applicable as a mitochondrion-targeted therapeutic drug for treating PD.…”

The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson’s Disease: A Promising Therapeutic Approach

“…Furthermore, DBYW was found to augment this process by enhancing the effects of DJ-1 on mitochondrial function through Akt phosphorylation. Additionally, DBYW enhances mitochondrial protection in PD by elevating cellular ATP content and decreasing the expression of ATP-sensitive potassium channel subunits [132].…”

Lycium barbarum Polysaccharide Ameliorates Heat-Stress-Induced Impairment of Primary Sertoli Cells and the Blood-Testis Barrier in Rat via Androgen Receptor and Akt Phosphorylation

“…Western Blot. Western blot was performed as described previously [35,36]. e total protein was extracted from SCs and transferred to polyvinyl difluoride (PVDF) membranes.…”